The invention relates in general to the field of microfluidics, microfluidic chips, and devices and methods to integrate receptors into a microfluidic device.
Microfluidics deals with the behavior, precise control and manipulation of small volumes of fluids that are typically constrained to micrometer-length scale channels and to volumes typically in the sub-milliliter range. Prominent features of microfluidics originate from the peculiar behavior that liquids exhibit at the micrometer length scale. Flow of liquids in microfluidics is typically laminar. Volumes well below one nanoliter can be reached by fabricating structures with lateral dimensions in the micrometer range. Reactions that are limited at large scales (by diffusion of reactants) can be accelerated. Finally, parallel streams of liquids can be accurately and reproducibly controlled, allowing for chemical reactions and gradients to be made at liquid/liquid and liquid/solid interfaces.
Microfluidic devices generally refer to microfabricated devices, which are used for pumping, sampling, mixing, analyzing and dosing liquids. Instead of using active pumping means, microfluidic devices are known, which use capillary forces for moving a liquid sample inside the microfluidic device. This makes the device simpler to operate and less expensive because there is no need for integrated or external (active) pump. However, particulates, contamination and other issues during manufacture can compromise capillary-based filling of the device.
Microfluidic devices for point-of-care diagnostics are devices meant to be used by non-technical staff, near patients or in the field, and potentially at home. Existing point-of-care devices typically require loading a sample onto the device and waiting a predefined time until a signal (usually optical or fluorescence signal) can be read. The signal originates from (bio)chemical reactions and relates to the concentration of an analyte in a sample. These reactions may take time and be difficult to implement because they require optimal timing, flow conditions of sample and accurate dissolution of reagents in the device. The reactions typically involve fragile reagents such as antibodies. Air bubbles may be created in the device, which can invalidate the test. In addition, debris in a device can block liquid flows. In devices where liquids must be split in parallel flow paths, filling may not occur at the same flow rate and this can bias or invalidate the tests.
In many analytical devices, receptors need be localized in an area of the device for binding and accumulating analytes in view of their detection. The localization of receptors is a challenging problem, in particular for mass manufacturing devices at a reasonable cost. In particular, when analytical devices need be closed, it is sometimes difficult to introduce receptors inside areas of the device. For capillary-active devices, an additional difficulty is to control the flow of solutions containing receptors and to avoid spreading of such solutions.
The localization of receptors can be done using lithography. Such a technique, however, is expensive, slow, and may lack flexibility and compatibility with fragile receptors such as antibodies. Spotting can also be used (e.g., inkjet, pin or quill spotting). However, such a technique leads to spreading of liquids, drying artefacts, aggregation and uneven distribution of receptors. Another technique commonly used is the local dispensing of a solution containing receptors on porous media such as paper or cellulose. This, however, leads to a lack of resolution and uneven receptor density that hinder multiplexing, miniaturization, and signal quantitation. Therefore, a solution is needed that makes it possible to ease the integration of receptors beads in an analytical device.